A Study in Participants With Epilepsy, to Evaluate the Pharmacokinetics, Safety and Tolerability of Oxcarbazepine on Padsevonil

UCB

Status and phase: Completed; Phase 1

Conditions: Epilepsy

Treatments: Drug: Padsevonil; Drug: Brivaracetam; Drug: Levetiracetam; Drug: Oxcarbazepine; Drug: Lamotrigine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03695094

UP0070

2018-001941-16 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to evaluate the effect of stable coadministered oxcarbazepine (OXC), on the pharmacokinetics (PK), safety, tolerability of padsevonil (PSL) and the plasma PK of PSL metabolites, UCB1431322-000 and UCB1447499-000, in study participants with epilepsy compared with study participants co-medicated with stable doses of levetiracetam (LEV), lamotrigine (LTG) or brivaracetam (BRV) therapy.

Enrollment: 31 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Study participant is male or female between 18 to 64 years of age, inclusive, with a diagnosis of epilepsy according to the International League Against Epilepsy (ILAE) classification

• Study participant is currently treated for epilepsy with stable doses of the following for at least 3 months:

  1. Inducers Group: Oxcarbazepine (OXC) (at least 1200 mg/day as monotherapy or in combination with brivaracetam (BRV) [up to 200 mg/day], levetiracetam (LEV) [at least 1 g/day] or lamotrigine (LTG) [at least 150 mg/day]); or
  2. Neutral (control) Group: LTG (at least 150 mg/day monotherapy or adjunctive to LEV or BRV), LEV (at least 1 g/day monotherapy or adjunctive to LTG), or BRV (up to 200 mg/day adjunctive to LTG)

• Study participant in the Inducers Group is taking OXC and has a trough OXC metabolite Mono Hydroxy Derivate (MHD) plasma level in the target range (≥12.0 to ≤35.0 mcg/mL)

• Study participant has clinical laboratory test results within the local reference ranges or values are considered as not clinically relevant by the Investigator and approved by the UCB Study Physician

• Study participant has a body mass index (BMI) of 18 to 35 kg/m², inclusive, with a body weight of at least 50 kg (male) or 45 kg (female)

• Female study participant has a negative serum pregnancy test at the Screening Visit and agrees to use an efficient form of contraception for the duration of the study (unless menopausal [defined as no menses for 12 months without an alternative medical cause]; a high follicle-stimulating hormone level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy). -Male study participant agrees that, during the study period, when having sexual intercourse with a woman of childbearing potential, he will use an efficient barrier contraceptive (condom plus spermicide) AND that the respective partner will use an additional efficient contraceptive method (eg, oral pills, intrauterine device, intrauterine hormone-releasing systems, or diaphragm, and spermicide)

Exclusion criteria

• Study participant has participated in another study of an investigational medication (or a medical device) within the last 3 months before screening (or 5 half-lives, whichever is longer) or is currently participating in another study of an investigational medication (or a medical device)
• Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol
• Study participant has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study
• Study participant has a history of status epilepticus during the last year
• Study participant has any clinically relevant electrocardiogram (ECG) finding at the Screening Visit or at Baseline
• Study participant has received any prescription or nonprescription medicines, including enzyme inhibitors or inducers, over the counter (OTC) remedies, herbal and dietary supplements (including St. John's Wort), or vitamins up to 2 weeks or 5 half-lives of the respective drug (whichever is longer) before the first administration of IMP and during the clinical part of the study, unless required to treat an Adverse event (AE). This does not include allowed antiepileptic drugs (AEDs) per the protocol, oral contraceptives not exceeding 30 μg ethinyl estradiol or postmenopausal hormone replacement therapy or implants, patches, or IUDs/IUSs delivering progesterone (for female study participants)

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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31 participants in 2 patient groups

Cohort 1

Experimental group

Description:

Cohort 1 (Inducers): Study participants on stable therapy with oxcarbazepine (OXC) either as monotherapy or adjunctive to levetiracetam (LEV), lamotrigine (LTG), or brivaracetam (BRV). OXC may be used as monotherapy or in combination with 1 or more of LEV, LTG, or BRV. Padsevonil (PSL) will be dosed to steady state and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.

Treatment:

Drug: Lamotrigine

Drug: Oxcarbazepine

Drug: Levetiracetam

Drug: Brivaracetam

Drug: Padsevonil

Cohort 2

Experimental group

Description:

Cohort 2 (Neutral): Study participants on stable therapy with lamotrigine (LTG), levetiracetam (LEV), or brivaracetam (BRV). LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. LTG or LEV may be used as monotherapy or in combination with each other. BRV may only be used in combination with LTG. Padsevonil (PSL) will be dosed to steady state (4.5 days) and the effect of background therapy on PSL pharmacokinetics will be assessed at steady state.

Treatment:

Drug: Lamotrigine

Drug: Levetiracetam

Drug: Brivaracetam

Drug: Padsevonil